Ginkgo biloba extract improves brain uptake of ginsenosides by increasing blood-brain barrier permeability via activating A1 adenosine receptor signaling pathway

Liang, Wenyi; Xu, Wei; Zhu, Jing; Yadong, Zhu; Gu, Quanlin; Li, Yuping; Guo, Caijuan; Huang, Yijian; Jing, Yu; Wang, Weixuan; Hu, Yinming; Zhao, Yanqun; Han, Bin; Bei, Weijian; Guo, Jiao

doi:10.1016/j.jep.2019.112243

Cited by 32 publications

(24 citation statements)

References 38 publications

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“…The spectrophotometric determination of EB and Dex stain accumulation in the brain is easy, reliable, and the most widely used technique to estimate BBB permeability [ 19 , 20 ]. The effects of SMG on BBB permeability were assessed by the extravasation of EB and Dex.…”

Section: Resultsmentioning

confidence: 99%

Rac1/Wave2/Arp3 Pathway Mediates Rat Blood-Brain Barrier Dysfunction under Simulated Microgravity Based on Proteomics Strategy

Yan¹,

Liu²,

Lv³

et al. 2021

IJMS

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The blood-brain barrier (BBB) is critical to maintaining central nervous system (CNS) homeostasis. However, the effects of microgravity (MG) on the BBB remain unclear. This study aimed to investigate the influence of simulated MG (SMG) on the BBB and explore its potential mechanism using a proteomic approach. Rats were tail-suspended to simulate MG for 21 days. SMG could disrupt the BBB, including increased oxidative stress levels, proinflammatory cytokine levels, and permeability, damaged BBB ultrastructure, and downregulated tight junctions (TJs) and adherens junctions (AJs) protein expression in the rat brain. A total of 554 differentially expressed proteins (DEPs) induced by SMG were determined based on the label-free quantitative proteomic strategy. The bioinformatics analysis suggested that DEPs were mainly enriched in regulating the cell–cell junction and cell–extracellular matrix biological pathways. The inhibited Ras-related C3 botulinum toxin substrate 1 (Rac1)/Wiskott–Aldrich syndrome protein family verprolin-homologous protein 2 (Wave2)/actin-related protein 3 (Arp3) pathway and the decreased ratio of filamentous actin (F-actin) to globular actin contributed to BBB dysfunction induced by SMG. In the human brain microvascular endothelial cell (HBMECs), SMG increased the oxidative stress levels and proinflammatory cytokine levels, promoted apoptosis, and arrested the cell cycle phase. Expression of TJs and AJs proteins were downregulated and the distribution of F-actin was altered in SMG-treated HBMECs. The key role of the Rac1/Wave2/Arp3 pathway in BBB dysfunction was confirmed in HBMECs with a specific Rac1 agonist. This study demonstrated that SMG induced BBB dysfunction and revealed that Rac1/Wave2/Arp3 could be a potential signaling pathway responsible for BBB disruption under SMG. These results might shed a novel light on maintaining astronaut CNS homeostasis during space travel.

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Section: Resultsmentioning

confidence: 99%

Rac1/Wave2/Arp3 Pathway Mediates Rat Blood-Brain Barrier Dysfunction under Simulated Microgravity Based on Proteomics Strategy

Yan¹,

Liu²,

Lv³

et al. 2021

IJMS

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“…The first criterion for being a neuroprotective drug is the permeability of blood-brain barrier (BBB). After oral administration of G. biloba extract, the ginsenosides could be identified and measured by liquid chromatography-mass spectrometry in the brain tissues of rats [ 38 , 39 ]. In addition, the absorption of ginsenosides by the brain cells was reported to be improved by activating adenosine signaling in a rat model [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…After oral administration of G. biloba extract, the ginsenosides could be identified and measured by liquid chromatography-mass spectrometry in the brain tissues of rats [ 38 , 39 ]. In addition, the absorption of ginsenosides by the brain cells was reported to be improved by activating adenosine signaling in a rat model [ 39 ]. In aged mouse model, oral administration of Rg 1 up-regulated the protein expression of brain-derived neurotrophic factor via activation of protein kinase A and cyclic adenosine monophosphate-response element-binding protein (CREB) phosphorylation in the brain, and thereafter the memory loss in aged mouse could be recovered [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Ginsenosides attenuate bioenergetics and morphology of mitochondria in cultured PC12 cells under the insult of amyloid beta-peptide

Kwan

Huang

Dong

et al. 2020

Journal of Ginseng Research

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Background Mitochondrial dysfunction is one of the significant reasons for Alzheimer's disease (AD). Ginsenosides, natural molecules extracted from Panax ginseng , have been demonstrated to exert essential neuroprotective functions, which can ascribe to its anti-oxidative effect, enhancing central metabolism and improving mitochondrial function. However, a comprehensive analysis of cellular mitochondrial bioenergetics after ginsenoside treatment under Aβ-oxidative stress is missing. Methods The antioxidant activities of ginsenoside Rb 1 , Rd, Re, Rg 1 were compared by measuring the cell survival and reactive oxygen species (ROS) formation. Next, the protective effects of ginsenosides of mitochondrial bioenergetics were examined by measuring oxygen consumption rate (OCR) in PC12 cells under Aβ-oxidative stress with an extracellular flux analyzer. Meanwhile, mitochondrial membrane potential (MMP) and mitochondrial dynamics were evaluated by confocal laser scanning microscopy. Results Ginsenoside Rg 1 possessed the strongest anti-oxidative property, and which therefore provided the best protective function to PC12 cells under the Aβ oxidative stress by increasing ATP production to 3 folds, spare capacity to 2 folds, maximal respiration to 2 folds and non-mitochondrial respiration to 1.5 folds, as compared to Aβ cell model. Furthermore, ginsenoside Rg1 enhanced MMP and mitochondrial interconnectivity, and simultaneously reduced mitochondrial circularity. Conclusion In the present study , these results demonstrated that ginsenoside Rg 1 could be the best natural compound, as compared with other ginsenosides, by modulating the OCR of cultured PC12 cells during oxidative phosphorylation, in regulating MMP and in improving mitochondria dynamics under Aβ-induced oxidative stress.

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“…The primary clinical application of EGb 761 includes improvement of cerebral and peripheral circulation as well as a positive effect on neurosensory dysfunction ( Yu et al, 2018 ; Singh et al, 2019 ; Kandiah et al, 2019 ; Liang et al, 2020 ). Numerous studies have confirmed the beneficial effects of EGb 761 and other standardized G. biloba leaf extracts on cognition and age-related problems with memory and concentration.…”

Section: The Use Of G Biloba In the Treatment And Prevention Of Admentioning

confidence: 99%

The Use of Ginkgo Biloba L. as a Neuroprotective Agent in the Alzheimer’s Disease

et al. 2021

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Alzheimer’s disease, a neurodegenerative disease, is one of the most common causes of dementia if elderly people worldwide. Alzheimer’s disease leads to the alienation of individuals and their exclusion from social and professional life. It is characterized mainly by the degradation of memory and disorientation, which occurs as a result of the loss of neuronal structure and function in different brain areas. In recent years, more and more attention has been paid to use in the treatment of natural bioactive compounds that will be effective in neurodegenerative diseases, including Alzheimer’s disease. G. biloba L. and its most frequently used standardized extract (EGb 761), have been used for many years in supportive therapy and in the prevention of cognitive disorders. The paper presents an overview of reports on the pathogenesis of Alzheimer’s disease, as well as a summary of the properties of G. biloba extract and its effects on the possible pathogenesis of the disease. By exploring more about the pathogenesis of the disease and the benefits of G. biloba extract for patients with Alzheimer’s disease, it will be possible to create an individualized therapeutic protocol to optimize the treatment.

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Ginkgo biloba extract improves brain uptake of ginsenosides by increasing blood-brain barrier permeability via activating A1 adenosine receptor signaling pathway

Cited by 32 publications

References 38 publications

Rac1/Wave2/Arp3 Pathway Mediates Rat Blood-Brain Barrier Dysfunction under Simulated Microgravity Based on Proteomics Strategy

Rac1/Wave2/Arp3 Pathway Mediates Rat Blood-Brain Barrier Dysfunction under Simulated Microgravity Based on Proteomics Strategy

Ginsenosides attenuate bioenergetics and morphology of mitochondria in cultured PC12 cells under the insult of amyloid beta-peptide

The Use of Ginkgo Biloba L. as a Neuroprotective Agent in the Alzheimer’s Disease

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